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51.
52.
David B. Kantor Cameron D. Palmer Taylor R. Young Yan Meng Zofia K. Gajdos Helen Lyon Alkes L. Price Samuela Pollack Stephanie J. London Laura R. Loehr Lewis J. Smith Rajesh Kumar David R. Jacobs Jr. Marcy F. Petrini George T. O’Connor Wendy B. White George Papanicolaou Kristin M. Burkart Susan R. Heckbert R. Graham Barr Joel N. Hirschhorn 《Human genetics》2013,132(9):1039-1047
Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry. 相似文献
53.
Unterreitmeier S Fuchs A Schäffler T Heym RG Frishman D Langosch D 《Journal of molecular biology》2007,374(3):705-718
Interactions of transmembrane helices play a crucial role in the folding and oligomerisation of integral membrane proteins. In order to uncover novel sequence motifs mediating these interactions, we randomised one face of a transmembrane helix with a set of non-polar or moderately polar amino acids. Those sequences capable of self-interaction upon integration into bacterial inner membranes were selected by means of the ToxR/POSSYCCAT system. A comparison between low/medium-affinity and high-affinity sequences reveals that high-affinity sequences are strongly enriched in phenylalanine residues that are frequently observed at the − 3 position of GxxxG motifs, thus yielding FxxGxxxG motifs. Mutation of Phe or GxxxG in selected sequences significantly reduces self-interaction of the transmembrane domains without affecting their efficiency of membrane integration. Conversely, grafting FxxGxxxG onto unrelated transmembrane domains strongly enhances their interaction. Further, we find that FxxGxxxG is significantly over-represented in transmembrane domains of bitopic membrane proteins. The same motif contributes to self-interaction of the vesicular stomatitis virus G protein transmembrane domain. We conclude that Phe stabilises membrane-spanning GxxxG motifs. This is one example of how the role of certain side-chains in helix-helix interfaces is modulated by sequence context. 相似文献
54.
用简并寡核苷酸探针筛选对虾白斑综合征病毒DNA多聚酶基因片段 总被引:1,自引:1,他引:1
根据一些病毒的DNA多聚酶氨基酸序列中特有的保守序列VYGDTD设计的简并寡核苷酸,经地高辛标记后与对虾白斑综合征病毒基因库克隆杂交,筛选出一段长度为707 bp的EcoR I基因片段,该片段在一个开放阅读框内.并含DNA多聚酶B家族特有的保守序列YGDTDS.经与基因库比较,其氨基酸序列与藻类DNA病毒科(Phycodnaviridae)的几株藻类病毒的DNA多聚酶片段有部分相似,因此推测该核苷酸片段为对虾白斑综合征病毒DNA多聚酶基因的部分序列. 相似文献
55.
Chang Gong Ziliang Cheng Yaping Yang Jun Shen Yingying Zhu Li Ling Wanyi Lin Zhigang Yu Zhihua Li Weige Tan Chushan Zheng Wenbo Zheng Jiajie Zhong Xiang Zhang Yunjie Zeng Qiang Liu R.Stephanie Huang Andrzej L.Komorowski Eddy S.Yang Fran?ois Bertucci Francesco Ricci Armando Orlandi Gianluca Franceschini Kazuaki Takabe Suzanne Klimberg Naohiro Ishii Angela Toss Mona P.Tan Mathew A Cherian Erwei Song 《中国科学:生命科学英文版》2022,65(11):2205-2217
Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR) to neoadjuvant chemotherapy(NAC). Here, we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS) in 755 HRpositive breast cancer patients(273, 265, and 217 in the training, internal, and external validation sets, respectively). This model,pres... 相似文献
56.
Sarah A. Cocherell Stephanie N. Chun Dennis E. Cocherell Lisa C. Thompson A. Peter Klimley Joseph J. CechJr. 《Environmental Biology of Fishes》2012,93(1):143-150
In regulated rivers, fluctuating water depths associated with pulsed discharges may strand small fish in side channels and
pools. Quantitative assessments of stranded fish are difficult in field studies (e.g., due to unknown effects of avian and
terrestrial vertebrate predators). To assess such lateral displacement and stranding on juvenile stream fishes, we designed,
constructed, and tested (with three species) a 2 × 1-m, lateral-displacement flume. The flume featured a main channel that
never drained and a raised, wide “floodplain” channel that alternately flooded, with a simulated pulse, and became dewatered.
The floodplain contained four pools, with different shapes and draining capacities, in which fish could become stranded as
the water level subsided. Fish-stranding rates (8%) in this relatively compact laboratory flume, after exposure to simulated
pulsed stream flows, were comparable to those observed in past investigations using larger, artificial streams. 相似文献
57.
58.
Manipulation of estrogen synthesis alters MIR202* expression in embryonic chicken gonads 总被引:1,自引:0,他引:1
Bannister SC Smith CA Roeszler KN Doran TJ Sinclair AH Tizard ML 《Biology of reproduction》2011,85(1):22-30
Tissue-specific patterns of microRNA (miRNA) expression contribute to organogenesis during embryonic development. Using the embryonic chicken gonads as a model for vertebrate gonadogenesis, we previously reported that miRNAs are expressed in a sexually dimorphic manner during gonadal sex differentiation. Being male biased, we hypothesised that up-regulation of microRNA 202* (MIR202*) is characteristic of testicular differentiation. To address this hypothesis, we used estrogen modulation to induce gonadal sex reversal in embryonic chicken gonads and analyzed changes in MIR202* expression. In ovo injection of estradiol-17beta at Embryonic Day 4.5 (E4.5) caused feminization of male gonads at E9.5 and reduced MIR202* expression to female levels. Female gonads treated at E3.5 with an aromatase inhibitor, which blocks estrogen synthesis, were masculinized by E9.5, and MIR202* expression was increased. Reduced MIR202* expression correlated with reduced expression of the testis-associated genes DMRT1 and SOX9, and up-regulation of ovary-associated genes FOXL2 and CYP19A1 (aromatase). Increased MIR202* expression correlated with down-regulation of FOXL2 and aromatase and up-regulation of DMRT1 and SOX9. These results confirm that up-regulation of MIR202* coincides with testicular differentiation in embryonic chicken gonads. 相似文献
59.
J Schmitt C Backes N Nourkami-Tutdibi P Leidinger S Deutscher M Beier M Gessler N Graf HP Lenhof A Keller E Meese 《BMC genomics》2012,13(1):379
ABSTRACT: BACKGROUND: Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared themiRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOPprotocol 2001. RESULTS: We did not find a significant difference between miRNA signature of both groups. However both, Wilmstumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. Thesignature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients afterchemotherapy an accuracy of 97.0%, each as compared to healthy controls. CONCLUSION: Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of fourweeks preoperative chemotherapy treatment. 相似文献
60.
María Fernanda Lammoglia Cobo Julia Ritter Regina Gary Volkhard Seitz Josef Mautner Michael Aigner Simon Vlkl Stefanie Schaffer Stephanie Moi Anke Seegebarth Heiko Bruns Wolf Rsler Kerstin Amann Maike Büttner-Herold Steffen Hennig Andreas Mackensen Michael Hummel Andreas Moosmann Armin Gerbitz 《PLoS pathogens》2022,18(4)
Reconstitution of the T cell repertoire after allogeneic stem cell transplantation is a long and often incomplete process. As a result, reactivation of Epstein-Barr virus (EBV) is a frequent complication that may be treated by adoptive transfer of donor-derived EBV-specific T cells. We generated donor-derived EBV-specific T cells by stimulation with peptides representing defined epitopes covering multiple HLA restrictions. T cells were adoptively transferred to a patient who had developed persisting high titers of EBV after allogeneic stem cell transplantation for angioimmunoblastic T-cell lymphoma (AITL). T cell receptor beta (TCRβ) deep sequencing showed that the T cell repertoire of the patient early after transplantation (day 60) was strongly reduced and only very low numbers of EBV-specific T cells were detectable. Manufacturing and in vitro expansion of donor-derived EBV-specific T cells resulted in enrichment of EBV epitope-specific, HLA-restricted T cells. Monitoring of T cell clonotypes at a molecular level after adoptive transfer revealed that the dominant TCR sequences from peptide-stimulated T cells persisted long-term and established an EBV-specific TCR clonotype repertoire in the host, with many of the EBV-specific TCRs present in the donor. This reconstituted repertoire was associated with immunological control of EBV and with lack of further AITL relapse. 相似文献